¹Assistant Professor, Department of Anaesthesia and Critical Care Medicine, ILBS (Institute of Liver and Biliary Sciences), New Delhi, INDIA.

²Assosiate Professor, Department of Anaesthesia, Mahadevappa Rampure Medical College, Gulbarga, Karnataka, INDIA.

Email: drsurabhi.anaesthesia@gmail.com, dr.yahya.imran@gmail.com

Complications which occurred as a result of patient’s conditions, mechanical ventilation or infusion of sedative agent were recorded in all the three groups. All statistical analyses were performed using INSTAT for windows. Continuous variables were tested for normal distribution by the Kolmogorov-Smirnov test. Data was expressed as either mean and standard deviation or numbers and percentages. All the data were compared with One-way Analysis of Variance (ANOVA).

RESULTS

30 patients each were randomly allocated to dexmedetomidine, propofol and midazolam group. Male predominance was noted, in all groups (dexmedetomidine, propofol and midazolam). Total M:F ratio was 1.3 : 1. Mean ± SD in age group in dexmedetomidine, propofol and midazolam group was 37.03 ± 12.75 years, 36.7 ± 12.18 years and 37.9 ± 12.48 years respectively.

Table 1: Age Distribution

The difference in respiratory rate, systolic blood pressure, systolic blood pressure, systolic blood pressure and SpO₂ among all the three groups calculated by ANOVA test is not statistically significant (P > 0.05).

Hypotension occurred in 6.4% patients in dexmedetomidine group, 14.22% in propofol group and 5% in midazolam group. Chest complications (nosocomial pneumonia, barotraumas) were the most common complication noted. 18% patients in dexmedetomidine group, 25.4% patients in propofol group, 21% patients in midazolam group had chest complications. Ventricular tachycardia (6.89%) occurred only in propofol group. Bradycardia occurred in 7.5% patients receiving dexmedetomidine. Intravenous line sepsis occurs more frequently with propofol 11.2% as compared to midazolam 8.9% and dexmedetomidine 7.3%. Prolonged sedation after cessation of sedation occurred most frequently with midazolam 11.34% than with propofol 3.11% and not seen in dexmedetomidine group. Bradycardia occurred in 7.5% patients receiving dexmedetomidine at the time of loading of drug.

Table 2: Complications

The mean length of stay (in days) for dexmedetomidine was 3.64 ± 0.95 days, for propofol is 4.12 ± 1.08 days and for midazolam is 4.22 ± 0.93 days. p value calculated by ANOVA test among all the three groups is >0.05 which is statistically not significant.

Table 3: Length of stay in ICU

DISCUSSION

The sedative and analgesic drugs commonly administered to ICU patients are derived from five distinct pharmacologic classes: Opiates (e.g. Fentanyl and remifentanil) , benzodiazepines (eg. Midazolam and lorazepam) isopropyl phenol anesthetics (eg. propofol), alpha 2 adrenoceptor agonists (e.g. dexmedetomidine) and dopamine blocking antipsychotic medications (eg. haloperidol and fluphenazine).¹ The common adverse effects of dexmedetomidine include hypotension, hypertension, nausea, bradycardia, atrial fibrillation, hypoxia and various atrioventricular blocks. Most of these adverse effects occur during or briefly after bolus dose of the drug, Omitting or reducing the loading dose can reduce adverse effects.⁶ In this study chest complications (nosocomial pneumonia, barotraumas) were the most common complication noted. 18% patients in dexmedetomidine groups, 25.4% patients in propofol group, 21% patients in midazolam group had chest complications. These findings were in accordance to Goodman NW et al.⁷ studied the ventilatory effects of propofol infusion and concluded that it leads to more chest complications. Bradycardia occurred in 7.5% patients receiving dexmedetomidine and the time of loading of the drug. This finding was in accordance with Eren G et at⁸ also noted that dexmedetomidine cause bradycardia. Prolonged sedation after cessation of sedation occurred most frequently with midazolam 11.34% than with propofol 3.11% and not seen in dexmedetomidine group. This finding in accordance with another study which authors found that patients receiving midazolam had a prolonged sedation time.⁹ None of the complications were statistically significant. Hypotension occurred 14.22% in propofol group 6.4% in dexmedetomidine group and 5% in midazolam group. More hypotension In propofol group is in accordance to study done by Larsen R et al..¹⁰ Dexmedetomidine should be used cautiously in patients with preexistent severe bradycardia and conduction problems, in patients with reduced ventricular functions (ejection fraction <30%), and in patients who are hypovolemic or hypotensive. Dexmedetomidine reduces sympathetic activity, resulting in lower blood pressure and reduced heart rate. These hemodynamic values return to baseline when the infusion is discontinued, Alternatively, treatment may include increasing the rate of IV fluid administration, elevation of the lower extremities or the use of presser agents.¹¹ Similar findings were noted in present study. De Cosmo G, et al.¹² noted that propofol causes hypotension, particularly in volume depleted patients, decreases cerebral oxygen consumption, reduces intracranial pressure and has potent anti-convulsant properties. Anger KE et al.¹³ noted no differences in the ICU length of stay and duration of mechanical ventilation between the propofol and dexmedetomidine groups, respectively. Hypotension, morphine use and nonsteroidal anti-inflammatory use occurred more during dexmedetomidine therapy versus propofol. Dexmedetomidine therapy resulted in a higher incidence of hypotension and analgesic consumption compared with propofol based sedation therapy. Propofol infusion syndrome is a rare but lethal syndrome associated with infusion of propofol at 4 mg/kg/hr. or more for 48 hours or longer. The clinical features of propofol infusion syndrome are acute refractory bradycardia leading to asystole, in the presence of one or more of the following: metabolic acidosis (base deficit >10 mmol/L), rhabdomyolysis, hyperlipidemia, and enlarged or fatty liver.¹⁴ Magarey JM¹⁵ concluded that that infusions of both midazolam and propofol appear to provide similar quality sedation, that extubation time and recovery time is shorter in patients sedated with propofol and that hemodynamic complications related to either drug regime are not usually clinically significant.  Hoy SM et al.¹⁶ concluded that intravenous dexmedetomidine is generally well tolerated when utilized in mechanically ventilated patients in an intensive care setting and for procedural sedation in non-intubated patients. Dexmedetomidine is associated with a lower rate of postoperative delirium than midazolam or propofol; it is not associated with respiratory depression. While dexmedetomidine is associated with hypotension and bradycardia, both usually resolve without intervention. Nseir S et al.¹⁷ concluded that prolongation of exposure to risk factors for infection, micro aspiration, gastrointestinal motility disturbances, microcirculatory effects, and immunomodulatory effects are main mechanisms by which sedation may favor infection in critically ill patients. Future studies should compare the effect of different sedative agents, and the impact of progressive opioid discontinuation compared with abrupt discontinuation on ICU acquired infection rates.

CONCLUSION

Dexmedetomidine is a satisfactory agent for sedation in ICU, safe to be used in the ICU. Dexmedetomidine provides hemodynamic stability and have no clinically important adverse effects on respiration.

REFERENCES

• Ostermann ME, Keenan SP, Seiferling RA, Sibbald WJ. Sedation in the intensive care unit: a systematic review. JAMA. 2000;283:1451–1459.
• Hall RI, Sandham D, Cardinal P, Tweeddale M, Moher D, Wang X, Anis AH, Study Investigators Propofol vs midazolam for ICU sedation: a Canadian multicenter randomized trial. Chest. 2001;119:1151–1159.
• Gommers D, Bakker J. Medications for analgesia and sedation in the intensive care unit: an overview. Crit Care. 2008;12 Suppl 3(Suppl 3):S4.
• Szumita PM, Baroletti SA, Anger KE, Wechsler ME. Sedation and analgesia in the intensive care unit: evaluating the role of dexmedetomidine. Am J Health Syst Pharm. 2007;64:37–44.
• Venn RM, Bryant A, Hall GM, Grounds RM.(2001) Effects of dexmedetomidine on adrenocortical function, and the cardiovascular, endocrine and inflammatory responses in postoperative patients needing sedation in the intensive care unit. Br 3 Anaesth 2001;86: 650-6.
• Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans, Anesthesiolo 2000;93:382- 394.\
• Goodman NW, Black AM, Carter JA Some ventilator effects of propofol as sole anaesthetic agent. Br J Anaesth 1987; 59:1497-1503.
• Eren O, Cukurova Z, Demir O, Hergunsel O, Kozanhan B, Emir P48 Comparison of dexmedetomidine and three different doses of Midazolam in preoperative sedation J Anaesthesiol Clin Pharmacol. 2011 Jul; 27(3):367-72.
• Yongfang Zhou, Xiaodong Jin, Yan Kang*, Guopeng Liang, Tingting Liu and Ni Deng. Midazolam and propofol used alone or sequentially for long-term sedation in critically ill, mechanically ventilated patients: a prospective, randomized study. Critical Care 2014, 18:R122
• Larsen R, Rathgeber J, Bagdahn A, Lange H, Rieke H. Effects of propofol on cardiovascular dynamics and coronary blood flow in geriatric patients. A comparison with etomidate. Anaesthesia. 1988 Mar;43 Suppl:25-31. doi: 10.1111/j.1365-2044.1988.tb09064.x. PMID: 3259092.
• Carollo, Dominic S; Nossaman, Bobby D; Ramadhyani, Usha Dexmedetomidine: a review of clinical applications, Current Opinion in Anaesthesiology: August 2008 - Volume 21 - Issue 4 - p 457-461
• De Cosmo G, Congedo E, Clemente A, Aceto P (2005) Sedation in PACU: the role of propofol. Curr Drug Targets 6:741–744. Review. 
• Anger KE, Szumita PM, Baroletti SA, Labrethe MJ, Panilcos I. Evaluation of dexmedetomidine versus propofol based sedation therapy in mechanically ventilated cardiac surgery patients at a tertiary academic medical center. Crit Pathw Cardiol 2010 Dec; 9(4): 221-6.
• Kam PC, Cardone D: Propofol infusion syndrome. Anaesthesia 2007; 62:690-701.
• Magarey JM. Propofol or midazolam which is best for the sedation of adult ventilated patients in intensive care units? A systematic review. Aust Crit Care. 2001 Nov;14(4):147-54. May; 80(5): 1057-72..
• Hoy SM, Keating GM. Dexmedetomidine: A review of its use for sedation in mechanically ventilated patients in an intensive care setting and for procedural sedation. Drugs. 2011 Jul 30; 71(1l): 1481-501.